Reversal of hypermethylation and reactivation of glutathione<i>S</i>-transferase pi 1 gene by curcumin in breast cancer cell line

Kumar, Umesh; Sharma, Ujjawal; Rathi, Garima

doi:10.1177/1010428317692258

Cited by 41 publications

(28 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HCC-38 is a triple-negative breast cancer (TNBC) cell line, UACC-3199 is estrogen receptor-negative/progesterone receptor-negative (ER -/PR -), and T47D is ER + /PR + . Based on previous studies (29,30,38,39), we treated the cells with 5 and 10 µM of curcumin. To investigate the effect of these curcumin concentrations on cell proliferation, we monitored cell proliferation in the presence of curcumin over a total period of 6 days.…”

Section: Curcumin Suppresses the Proliferation Of Hcc-38 Uacc-3199 mentioning

confidence: 99%

“…Several studies have shown that this herb can exert anticancer effects, on breast cancer in particular, by targeting various signaling pathways (27). Furthermore, it has been reported that curcumin can function as a DNA methylation inhibitor in breast cancer cells (28)(29)(30)(31)(32). Nevertheless, curcumin's potential as a DNA methylation inducer remains to be fully explored.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Curcumin induces re‑expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines

et al. 2020

View full text Add to dashboard Cite

Restoration of normal DNA promoter methylation and expression states of cancer-related genes may be an option for the prevention as well as the treatment of several types of cancer. Constitutional promoter methylation of BRCA1 DNA repair associated (BRCA1) gene is linked with a high risk of developing breast and ovarian cancer. Furthermore, hypomethylation of the proto-oncogene γ synuclein (SNCG) is associated with the metastasis of breast and ovarian cancer and reduced disease-free survival (DFS). In the present study, we evaluated the potential of curcumin to re-express hypermethylated BRCA1 and to suppress hypomethylated SNCG in triple-negative breast cancer (TNBC) cell line HCC-38, the estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) cell line UACC-3199, and the ER + /PR + cell line T47D. The cells were treated with 5 and 10 µM curcumin for 6 days and with 5-aza-2'-deoxycytidine (5'-aza-CdR) for 48 h. Methylation-specific PCR and bisulfite pyrosequencing assays were used to assess DNA promoter methylation while gene expression levels were analyzed using quantitative real-time PCR and immunoblotting. We found that curcumin treatment restored BRCA1 gene expression by reducing the DNA promoter methylation level in HCC-38 and UACC-3199 cells and that it suppressed the expression of SNCG by inducing DNA promoter methylation in T47D cells. Notably, 5'-aza-CdR restored BRCA1 gene expression only in UACC-3199, and not in HCC-38 cells. Curcumin-induced hypomethylation of the BRCA1 promoter appears to be realized through the upregulation of the ten-eleven translocation 1 (TET1) gene, whereas curcumin-induced hypermethylation of SNCG may be realized through the upregulation of the DNA methyltransferase 3 (DNMT3) and the downregulation of TET1. Notably, miR-29b was found to be reversely expressed compared to TET1 in curcumin-and 5'-aza-CdR-treated cells, suggesting its involvement in the regulation of TET1. Overall, our results indicate that curcumin has an intrinsic dual function on DNA promoter methylation. We believe that curcumin may be considered a promising therapeutic option for treating TNBC patients in addition to preventing breast and ovarian cancer, particularly in cancer-free females harboring methylated BRCA1.

show abstract

Section: Curcumin Suppresses the Proliferation Of Hcc-38 Uacc-3199 mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Curcumin induces re‑expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Earlier gene candidate studies performed in murine RAW 264.7 macrophage cells and TRAMP C1 prostate cancer cells delivered evidence for curcumin‐mediated demethylation and activation of Nrf2 , a potent activator of antioxidant pathways (Khor et al, ). Another member of the antioxidant network, GSTP1 , was also found to be demethylated and activated upon exposure of breast cancer cells to curcumin (Kumar, Sharma, & Rathi, ). Furthermore, Maugeri et al () reported up‐regulation of DNMT1 expression and activity along with oxidative stress induced by chronic high glucose levels in a cellular model of diabetic retinopathy (Maugeri et al, ).…”

Section: Interrelationship Between Antioxidant Properties and Dna Metmentioning

confidence: 99%

“…Earlier gene candidate studies performed in murine RAW 264.7 macrophage cells and TRAMP C1 prostate cancer cells delivered evidence for curcumin-mediated demethylation and activation of Nrf2, a potent activator of antioxidant pathways (Khor et al, 2011). Another member of the antioxidant network, GSTP1, was also found to be demethylated and activated upon exposure of breast cancer cells to curcumin (Kumar, Sharma, & Rathi, 2017 CDKN2A at a non-invasive breast cancer stage , PTEN and RARβ2 in breast cancer cells (Lubecka-Pietruszewska et al, 2015), and RARβ, CDH1, DAPK1, and GSTP1…”

Section: A Link Between Antioxidant Properties Of Curcumin and Curcmentioning

confidence: 99%

Dietary antioxidants remodel DNA methylation patterns in chronic disease

Beetch

Harandi-Zadeh

Shen

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

Chronic diseases account for over 60% of all deaths worldwide according to the World Health Organization reports. Majority of cases are triggered by environmental exposures that lead to aberrant changes in the epigenome, specifically, the DNA methylation patterns. These changes result in altered expression of gene networks and activity of signalling pathways. Dietary antioxidants, including catechins, flavonoids, anthocyanins, stilbenes and carotenoids, demonstrate benefits in the prevention and/or support of therapy in chronic diseases. This review provides a comprehensive discussion of potential epigenetic mechanisms of antioxidant compounds in reversing altered patterns of DNA methylation in chronic disease. Antioxidants remodel the DNA methylation patterns through multiple mechanisms, including regulation of epigenetic enzymes and chromatin remodelling complexes. These effects can further contribute to antioxidant properties of the compounds. On the other hand, decrease in oxidative stress itself can impact DNA methylation delivering additional link between antioxidant mechanisms and epigenetic effects of the compounds. Linked Articles This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc

show abstract

“…В умовах in vitro у клітинах лінії раку молочної залози MCF-7 куркумін інгібував метилювання промотора GSTP1 шляхом блокування каталітичного тіола-ту ДНК метилтрансферази 1 і це призводило до повторної експресії протеїну GSTP1 (Kumar et al, 2017).…”

unclassified

Glutathione transferase and mammary tumors

Fedets

Kurlyak

2019

SMLNUVMB

View full text Add to dashboard Cite

The analysis of publications from the last 5 years is presented in this review. These articles describe the relationship of glutathione transferase (GST) with mammary tumors. Most of these works are dedicated to investigating the genotypic relationship between GST and neoplasms in human. The most common are single nucleotide polymorphism of GSTP1 Val105Ile (rs1695) and gene deletions GSTM1 and GSTT1. Several publications describe polymorphisms of GSTM3(rs4970737), GSTM4 and GSTA5. These polymorphisms (especially GSTP1 Val105Ile) are associated with the risk of mammary tumors, overall survival and relapse in patients of some ethnic groups. This is as a result of reduced enzymatic activity of GST and disturb of ability to detoxify substrates. Some studies demonstrate that single nucleotide polymorphism of GSTP1 Val105IIe is associated with a better response to chemotherapy and overall survival of patients, but no association with genotypes of GSTM1 and GSTT1. The injections of carcinogenic compounds into the tissue of mammary gland or its feeding to rats leed to decrease of GST activity and to development of tumors. The increased expression of GST in breast cancer cell lines leeds to increase of the resistance of these cells against various chemical compounds therefore the enzyme catalyzes the binding of these compounds to glutathione and this prevent their negative effects and is necessary for the formation of conjugates. Such increased expression of GST indicates on the resistance of breast cancer cell lines in particular to the action of drugs, which reduces their therapeutic effect. This is shown on cell lines BT474, MCF-7, MCF-7/ADR, MCF-7/ADR-1024, MCF-10A, MDA-MB-231, MDA-MB-468 and T47D. Chemical compounds (including antitumor drugs), that reduce the activity and/or expression of GST, can have a cytotoxic effect on these cells. Mammary tumors associated with epigenetic changes that do not change the sequence of nucleotides in GST genes. The methylation of the GSTP1 promoter decreases an expression of protein in mammary tissue and increases a risk of cancer in different ethnic groups. Compounds increase the level of expression of genes when they are able to lower the level of methylation or to affect demethylation. Polymorphisms of GST genes, their association with response to chemotherapy and overall survival of patients, expression of GST and it dependence on the action of anticancer drugs, methylation of GST promoter are associated with diagnosis, prognosis, and treatment of mammary neoplasms.

show abstract

Reversal of hypermethylation and reactivation of glutathioneS-transferase pi 1 gene by curcumin in breast cancer cell line

Cited by 41 publications

References 18 publications

Curcumin induces re‑expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines

Curcumin induces re‑expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines

Dietary antioxidants remodel DNA methylation patterns in chronic disease

Glutathione transferase and mammary tumors

Contact Info

Product

Resources

About